Our current studies on human thyroid carcinoma are aimed at improving radioiodine therapy of this disease. The effectiveness of such therapy is limited by the rapid iodine release from the tumor after its incorporation into thyroglobulin. Until recently, the only agent known to block release of organic iodine from the thyroid gland was iodine ion. However, this agent is not used during I131 therapy because it also would diminish tumor uptake. In previous studies we showed that lithium ion blocks the release of iodine from the normal thyroid gland and is effective in the therapy of hyperthyroidism for the same reason. We therefore investigated the blocking effect of Li ion in a patient with highly functional thyroid carcinoma. Li ion decreased the disappearance rate of a tracer dose of I131 from the whole body and from a tumor mass from control values of 0.126 and 0.122/day to .09 and .049/day, respectively. Although this was expected to increase the therapeutic/toxic ratio of I131, an unanticipated increase in blood I131 followed a subsequent therapy dose, presumably due to increased tumor radiation, and resulted in significant bone marrow depression. Thus, Li ion is effective as an adjunct in I131 therapy but must be used with caution. The demonstrated blocking effect of Li ion will also be employed as an adjunct to the use of TRH in enhancing tumor uptake prior to I131 therapy.